A cross-sectional analysis of data from the National Health and Nutrition Examination Survey (NHANES) reported a significant association between sleep deficiency and a higher risk of age-related macular degeneration (AMD).1

To further clarify this relationship, the investigative team from Yan’an People’s Hospital performed two-sample Mendelian randomization and found the results were supported: sleep deprivation increased the risk of early AMD and advanced AMD could increase the risk of sleep deprivation.

“The findings could be a reminder that we ophthalmologists should pay more attention to individuals with sleep disorders,” Investigators wrote.

Sleep problems in those with a neurodegenerative disease, such as AMD, are frequently observed and are a hallmark of an aging population. This cross-sectional analysis, led by Haihui Li, explored the potential role of sleep abnormalities in the pathogenesis of AMD.

Observational studies are known to be prone to reverse causation, residual confounding, and selective bias. While randomized clinical trials are reliable and allow for robust conclusions, they can be costly and time-consuming to conduct. A Mendelian randomization approach could allow for the assessment of clinically associated variables and overcome biases in data.2

Using survey data from the 2005-2008 NHANES, the analysis identified 5481 participants aged ≥40 years. Li and colleagues implemented bidirectional two-sample randomization to determine causation from independent and large genome-wide association studies of sleep duration and AMD. Summary-level statistics for early AMD included 105,248 participants in a European population (14,034 early AMD; 71,214 controls); the International AMD Genomics Consortium included 16,144 patients with advanced AMD and 17,832 control patients.

Abnormal sleep deprivation was defined as insufficient/short sleep duration (<7 hours per night), normal (7-8 hours per night), or excessive/long sleep duration (≥9 hours per night). The team analyzed the association between sleep duration and AMD using logistic regression models. In the Mendelian randomization analysis, the primary method was the random-effect inverse-variance weighted method.

In the cross-sectional analysis, investigators observed a significantly positive association between short sleep duration and AMD (odds ratio [OR], 1.364; 95% CI, 1.058 - 1.941; P = .036), after adjusting for multiple covariates.

In Mendelian randomization, results showed that short sleep duration causally increases the risk of early AMD (β = 0.102; 95% CI, 0.008 - 0.195; IVW-derived P = .003). In addition, investigators found advanced AMD causally increases the risk of short sleep duration (β = .002; 95% CI, 0.001 - 0.003; IVW-derived P = 6.70E-05).

Although the study team attempted to correct potential confounders, they indicated additional sleep factors, including shift workers and those with young children, were not taken into consideration in the analysis. They also suggest light exposure, a factor frequently associated with sleep duration, could be a confounder when evaluating the association between sleep duration and AMD, but a loss of data kept it out of the analysis.

“Findings from this study only reveal a significant association between short sleep duration and AMD, but not the underlying mechanisms, which call for further research,” investigators wrote.


  1. Lei S, Liu Z, Li H. Sleep duration and age-related macular degeneration: a cross-sectional and Mendelian randomization study. Front Aging Neurosci. 2023;15:1247413. Published 2023 Aug 22. doi:10.3389/fnagi.2023.1247413
  2. Davey Smith G., Hemani G. (2014). Mendelian randomization: genetic anchors for causal inference in epidemiological studies. Hum. Mol. Genet. 23 R89–R98. 10.1093/hmg/ddu328

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